FGF-2 for Ear Drum Perforation

Overseen By Ashley Feng

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Radiation, Corticosteroids, Immunosuppressants, Chemotherapy

Disqualifiers: Otitis media, Immunosuppressed, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called FGF-2 (Fibroblast Growth Factor 2) to heal chronic ear drum holes that haven't closed on their own. Participants will receive either the FGF-2 treatment or a placebo (a harmless fake treatment) to determine which is more effective at closing the holes. If the initial treatment doesn't work, those on the placebo can later try FGF-2. Individuals with a dry ear drum perforation for at least six months, but no active ear infections, might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. The trial excludes participants who are taking radiation therapy, corticosteroids, immunosuppressive agents, chemotherapy, or systemic antibiotics.

Will I have to stop taking my current medications?

The trial requires that participants not be taking certain medications, such as radiation therapy, corticosteroids, immunosuppressive agents, chemotherapy, or systemic antibiotics. If you are on any of these, you would need to stop them to participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using FGF-2 on eardrum perforations is generally safe. One study found that applying FGF-2 to damaged eardrums did not cause serious side effects. The most common issue reported was fluid discharge from the ear. Studies reviewed have found no long-term negative effects. This treatment is under study for its potential to help close chronic eardrum perforations that do not heal on their own. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike most treatments for eardrum perforation, which often involve surgical repair or waiting for natural healing, FGF-2 is unique because it uses a growth factor to stimulate tissue regeneration directly. Researchers are excited about FGF-2 because it targets the body's natural healing processes, potentially speeding up recovery and reducing the need for surgery. This approach may offer a less invasive and faster alternative to current treatments, making it an exciting development in otolaryngology.

What evidence suggests that FGF-2 might be an effective treatment for ear drum perforation?

Research has shown that FGF-2, which participants in this trial may receive, holds promise for healing chronic holes in the eardrum. Previous studies demonstrated very positive results, with FGF-2 effectively closing these holes. Over 200 patients experienced successful eardrum healing and improved hearing after using FGF-2. Additionally, FGF-2 has proven safe, with no serious side effects reported. These findings suggest that FGF-2 could be a strong option for treating eardrum holes that don't heal on their own. ^{1 2 4 6 7}

Who Is on the Research Team?

David Friedmann, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

Adults over 18 with chronic ear drum perforations lasting at least 6 months can join. They must not be pregnant, agree to birth control use, and have no severe diabetes, ear shape abnormalities, active middle ear infections or recent substance abuse. Those on certain medications like antibiotics or with conditions affecting participation are excluded.

Inclusion Criteria

Any person of child-bearing potential, must have a negative beta-HCG test and must agree to use an adequate form of birth control throughout the clinical trial.

I have had a hole in my eardrum for at least 6 months.

Exclusion Criteria

Active alcohol or drug abuse within 6 months prior to study entry

My tissue damage is due to a burn or radiation therapy.

Subjects having any granulation or soft tissue density due to inflammation, or infection in mastoid antrum determined by CT scanning (Temporal bone CT scanning)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants are randomized to receive FGF-2 or placebo treatment up to 3 treatments

Up to 134 days

Unblinded Crossover

Participants who failed placebo treatments crossover to receive unblinded FGF-2 for up to 3 treatments

Up to 134 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FGF-2
• Placebo

Trial Overview The trial is testing FGF-2's ability to heal long-term tympanic membrane (ear drum) perforations versus a placebo. It's double-blinded: neither doctors nor patients know who gets real treatment. If the placebo fails after three tries, those patients get FGF-2 in an unblinded crossover phase.

How Is the Trial Designed?

Group I: Human Fibroblast Growth Factor-2 (FGF-2) Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

In a phase 2 clinical trial involving 54 patients with chronic tympanic membrane perforations, fibroblast growth factor-2 (FGF-2) treatment did not show a statistically significant improvement in closure rates compared to a placebo, with closure rates of 57.5% for FGF-2 and 71.4% for placebo.

There were no significant differences in hearing outcomes between the FGF-2 and placebo groups, indicating that FGF-2 may not be an effective treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical fibroblast growth factor-2 for treatment of chronic tympanic membrane perforations. Santos, F., Shu, E., Lee, DJ., et al.[2022]

In a study of 138 patients with traumatic tympanic membrane perforations, the use of fibroblast growth factor-2 (FGF-2) delivered via Gelfoam patches resulted in a significantly higher closure rate of 97.9% compared to 70.7% in the observation group.

FGF-2 plus Gelfoam patches not only improved closure rates but also reduced closure times to an average of 15.7 days, making it a promising minimally invasive treatment option for tympanic membrane perforations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus. Jin, ZH., Dong, YH., Lou, ZH.[2018]

In a study of 86 patients with large traumatic tympanic membrane perforations, both epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) significantly improved closure rates compared to an observation-only group, with closure rates of 86.2% and 89.3% respectively versus 72.4% for observation.

The average time for closure was significantly shorter in the EGF and bFGF groups compared to the observation group, indicating that these growth factors can accelerate healing, although there was no significant difference in effectiveness between EGF and bFGF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study on the effects of EGF and bFGF on the healing of human large traumatic perforations of the tympanic membrane. Zhengcai-Lou, ., Zihan-Lou, ., Yongmei-Tang, .[2016]

Topical application of 400 ng of fibroblast growth factor (FGF) significantly accelerated the healing of tympanic membrane perforations in rats, reducing the closure time from 8.8 days in untreated ears to 6.1 days.

Higher doses of FGF led to complications such as myringitis, while a dose of 200 ng did not show any significant difference compared to the placebo, indicating that the optimal dose for healing is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor improves the healing of experimental tympanic membrane perforations. Mondain, M., Saffiedine, S., Uziel, A.[2019]

Fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) both demonstrated effective closure rates for tympanic membrane (TM) regeneration, with FGF2 showing closure rates of 55%-100% for acute perforations compared to 10%-62.5% in controls, while EGF showed 30.3%-100% for chronic perforations.

EGF was found to be more effective for acute TM perforations, whereas FGF2, especially when combined with biological scaffolds, was superior for chronic perforations, although it had higher rates of reperforation over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGF2 and EGF for the Regeneration of Tympanic Membrane: A Systematic Review. Lou, Z., Lou, Z., Jiang, Y., et al.[2022]

In a mouse model of chronic tympanic membrane perforations, heparin binding epidermal growth factor-like growth factor (HB-EGF) demonstrated a significantly higher healing rate (83.3%) compared to fibroblast growth factor 2 (FGF2, 31.6%) and epidermal growth factor (EGF, 15.8%).

The study suggests that HB-EGF not only promotes better healing but also results in tympanic membranes that resemble normal structure, indicating its potential as an effective nonsurgical treatment option for chronic TM perforations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model. Santa Maria, PL., Weierich, K., Kim, S., et al.[2018]

The application of basic fibroblast growth factor (bFGF) significantly improves the closure rate of tympanic membrane (TM) perforations, with an odds ratio of 7.33 based on a meta-analysis of 14 studies involving 1,072 participants.

While bFGF treatment accelerates healing time for TM perforations, it does not show a significant impact on improving hearing, indicating its primary benefit is in promoting tissue repair rather than auditory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis. Huang, J., Teh, BM., Eikelboom, RH., et al.[2022]

In a study of 147 patients with traumatic tympanic membrane perforations, treatment with basic fibroblast growth factor (bFGF) resulted in a high healing rate of 98.0%, regardless of the timing of treatment within the first four weeks after injury.

The average healing times for small perforations were significantly shorter when treated within 8 to 14 days after injury, indicating that bFGF is an effective treatment option for tympanic membrane injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the effectiveness of basic fibroblast growth factor treatment on traumatic perforation of the tympanic membrane at different time points. Lou, Z., Tang, Y., Wu, X.[2013]

Fibroblast growth factor-2 has shown a high success rate (89.3-100%) in regenerating tympanic membrane perforations in humans, with an average closure time of about 2 weeks, indicating its efficacy in treating both acute and chronic cases.

When combined with Gelfoam, fibroblast growth factor-2 achieved an impressive success rate of 83-98.1% for chronic perforations, compared to only 10% for those treated with gelatine sponge alone, highlighting its potential advantages over traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regeneration of the tympanic membrane using fibroblast growth factor-2. Lou, ZC., Lou, ZH., Xiao, J.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7444771/

Topical fibroblast growth factor‐2 for treatment of chronic ... As noted above, several human studies using FGF‐2 to promote tympanic membrane perforation closure showed highly promising results. We must ask ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02307916

Fibroblast Growth Factor Regeneration of Tympanic ... The goal is to determine the safety and efficacy of Fibroblast Growth Factor-2 (FGF-2) in the closure of chronic tympanic membrane perforations (TMP).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6036947/

and long-term adverse effects of FGF-2 on tympanic ... This study suggests that the topical application of fibroblast growth factor-2 to human traumatic tympanic membranes is safe.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0385814623001773

Outcomes of regenerative treatment for over 200 patients ... Our results showed that RT-TMP had high success rates for TMP closure and good hearing improvement and produced no severe complications that could affect ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0196070923001680

Comparative study of fibroblast growth factor 2 and ... This study suggested that both FGF2 and OFLX significantly shortened the mean closure time and improved the closure rate compared with spontaneous healing.

6. withpower.com withpower.com/trial/phase-3-tympanic-membrane-perforation-7-2021-6dfb4

FGF-2 for Ear Drum Perforation · Info for Participants The safety data for FGF-2 in treating tympanic membrane perforations includes findings from various studies. In a study on rats, a higher dose of FGF led to a ...

7. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/fgf_perfs

Do you have an ear drum perforation that has persisted for ... The goal of this clinical trial is to compare the application of fibroblast growth factor 2 (FGF2) with normal saline for the healing of chronic tympanic ...